Diminished autonomic nervous system responsiveness in rheumatoid arthritis of recent onset

To investigate responsiveness of the autonomic nervous system in rheumatoid arthritis (RA) of recent onset. 21 patients (17 women, mean age 55.7 years) and 20 healthy controls (16 women, mean age 52.7 years) were subjected to 4 tasks eliciting divergent autonomic reactions: film watching, mild physical exercise, cognitive discrimination, and the Stroop color-word interference test. Changes in heart rate, diastolic (DBP) and systolic (SBP) blood pressure, and skin conductance relative to pretask baseline values were computed and related to erythrocyte sedimentation rate, pain, mobility, and dexterity. Mean autonomic levels of patients were normal, as well as autonomic responses to film watching and mild physical exercise. Diminished autonomic responses were observed during cognitive discrimination and during the Stroop test. Blood pressure responses were negatively related to pain severity, but positively to impaired dexterity. Diminished autonomic nervous system response is observed in RA of recent onset, most clearly in patients with more severe pain. This suggests that it is associated with primary pathophysiological mechanism

Experimental stress and immunological reactivity: a closer look at perceived uncontrollability

Although stressor uncontrollability has been shown to suppress immune responses in animals and for human subjects, the results have been inconsistent. We reanalyzed results of our previous study regarding stress-related immune deviation in man, to establish whether perceived uncontrollability of an acute stressor acts as a co-determinant in the observed changes in immunological parameters. Three types of cognitive reactions to an acute interpersonal stressor were assessed: "motivation," "uncontrollability," and "guiltiness." Stress-induced changes in the number of several types of immune cells in peripheral blood and proliferative responses of lymphocytes to antigens and mitogens were assessed. In comparison with control subjects and with subjects perceiving high control over the experimental stress situation, the subject perceiving low control showed a stressor-induced decrease in the number of T helper cells. Reversely, subjects perceiving high control showed an increase in the number of B cells as opposed to the other two groups. The effects of perceived uncontrollability could not be accounted for by mood changes, but they were related to previously experienced life stress. Perceived uncontrollability of an acute stressor can have immuno-modulating effects over and above those of the stressor per s

Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus:a randomised controlled trial

Objective Dehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are common in SLE. The present work investigates the effects of DHEA administration on fatigue, well-being and functioning in women with inactive SLE. Methods In a double-blind, randomised, placebo-controlled study, 60 female patients with inactive SLE received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being and physical functioning. Assessments were made before treatment, after 3, 6 and 12 months on medication, and 6 months after cessation of treatment. Results Patients from the DHEA and placebo group improved on general fatigue (p <0.001) and mental wellbeing (p = 0.04). There was no differential effect of DHEA. The belief that DHEA had been used was a stronger predictor for improvement of general fatigue than the actual use of DHEA (p = 0.04). Conclusions The trial does not indicate an effect of daily 200 mg oral DHEA on fatigue and well-being, and therefore DHEA treatment is not recommended in unselected female patients with quiescent SLE

Influence of life stress on immunological reactivity to mild psychological stress

This study investigated the effects of self-reported life stress and locus of control on reactivity of several immune parameters to a mild and short-lasting interpersonal stressor. Subjects were 86 male teachers aged 24 to 55 years. Immune reactivity was defined as changes in numbers of monocytes. T-lymphocytes and subsets, HLA-DR+ cells, and NK cells as well as changes in (in vitro) proliferative responses of peripheral blood lymphocytes to the antigens PHA and PWM. Multiple regression analysis was used to study the interaction effects of life stress and locus of control by experimental condition on immune reactivity. Life stress, but not locus of control, influences reactivity of the immunological parameters to the stressor. In particular, high numbers of daily hassles were associated with stressor-induced decreases in numbers of T cells and NK cells in peripheral blood. On the other hand, numbers of HLA-DR+ cells in high life stress scorers decreased only slightly during the stressor, whereas they increased in the control condition. The findings suggest that accumulated life stress is related to reactivity of immunological parameters to subsequent experimental stress. Possible physiological explanations and implications of these effects are discusse

Effect of dehydroepiandrosterone administration on fatigue, well-being, and functioning in women with primary Sjogren syndrome:a randomised controlled trial

Objective: Dehydroepiandrosterone (DHEA) administration has been reported to improve fatigue, psychological distress, and physical disability. These are common features of primary Sjogren syndrome (pSS). We investigated the effects of DHEA administration on fatigue, well-being, and functioning in women with pSS. Methods: In a double-blind, randomised placebo-controlled clinical trial, 60 female patients with pSS received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being, and physical functioning. In addition, pain, sicca complaints and disease activity parameters were measured. Patients were assessed before treatment, after 3, 6, and 12 months on study medication, and 6 months after cessation of treatment. Results: Patients from both the DHEA-and placebo-treated group improved on general fatigue (p Conclusions: Our study does not support a superior effect of DHEA over placebo in female patients with pSS. Both DHEA and placebo induce improvement of fatigue and well-being. This may suggest possibilities for cognitive behavioural interventions

Fatigue in patients with systemic lupus erythematosus: the role of dehydroepiandrosterone sulphate

Fatigue is a major problem in systemic lupus erythematosus (SLE), but the physiological substrate of this fatigue is largely unclear. To examine if low levels of dehydroepiandrosterone (DHEA) and its sulphate DHEAS play a role in SLE fatigue, we compared: 1) DHEAS levels and fatigue between 60 female patients with SLE with low disease activity (31 using, 29 not using prednisone) and 60 age-matched healthy women, and 2) fatigue between patients with SLE with low and normal DHEAS levels. Serum DHEAS levels were determined with an Advantage Chemiluminescense System. The Multidimensional Fatigue Inventory (MFI) was used to assess fatigue. Patients were more fatigued (p = 0.39). Patients with low DHEAS levels not using prednisone reported less fatigue than those with normal DHEAS levels (

Effects of experimental psychological stress on distribution and function of peripheral blood cells

Fifty male subjects (aged 24 to 55 years) were subjected to a mild and potentially uncontrollable interpersonal stress situation. They were asked to solve a difficult puzzle. Subsequently they were requested to explain their solution to "another subject," actually a confederate to the researchers. The confederate frustrated the subjects' explanation efforts. Care was taken that neither solving nor explaining of the puzzle was successful. The experimental situation induced mild psychological strain as documented by mood changes in the experimental group when compared with a control group of 36 male subjects. Peripheral blood was drawn by an indwelling catheter just before, directly after, 15 minutes after, and 30 minutes after the stress situation. Numbers of leukocytes, lymphocytes, monocytes, T-cell subsets, natural killer (NK) cells, and B-cells were determined. As functional assays we used in vitro proliferative responses of T- and B-cells to mitogenic stimulation (PHA and PWM) and to an antigen cocktail. The potential influences of health- and biobehavioral variables were taken into account in the analyses, as well as incidental differences in initial mood or immunological baseline. The results replicated and expanded on previous research. In contrast to controls, experimental subjects showed a significant increase in numbers of NK cells after the stress-period, returning to baseline values after 15 minutes of rest. A similar effect was shown on T-suppressor/cytotoxic cells and, inversely, on T-helper/suppressor ratio, but these effects could be attributed to changes in the numbers of CD8+CD57+ cells. No effects were observed on proliferation. From the results we conclude that the effects of a short lasting mild psychological stressor are mainly restricted to cells of the NK cell populatio

Experimentally challenged reactivity of the hypothalamic pituitary adrenal axis in patients with recently diagnosed rheumatoid arthritis

There is evidence that the hypothalamic pituitary adrenal (HPA) axis is subresponsive in patients with rheumatoid arthritis (RA). We assessed HPA axis responses to experimental stressors mimicking daily life challenges in patients with RA to determine whether HPA axis activity is associated with Th1 and Th2 activity. ACTH and cortisol responses in reaction to the succession of a bicycle ergometer task, a cold pressor task, and a computerized Stroop Color-Word interference test, as well as basal Th1 and Th2 cell activity, were assessed in 29 patients (21 female, 8 male) with recently diagnosed RA (mean disease duration 29 wks, range 5-69), mean age 55.7 years, none receiving glucocorticoid treatment, and 30 (20 female, 10 male) healthy age and sex matched controls (mean age 54.1 yrs). Mean ACTH and cortisol levels did not differ between the groups (p > 0.10). Patients tended to have a less pronounced ACTH response (F2.50 = 2.7, p = 0.08) and had a significantly smaller cortisol response (P F2.50 = 6.1, p 0.19) with basal interferon-gamma and interleukin 4 as reflections of Th1 and Th2 cell activity, respectively. HPA axis activity was not linked to current disease activity. Our findings show reduced HPA axis responsiveness in RA patients with recent diagnosis receiving longterm medication that is suggested to be located both at a hypothalamic/pituitary and at an adrenal level. It appears that common HPA axis activity accomplishes low amounts of cortisol release, which makes it difficult to determine an influence of endogenous cortisol changes on the Th1/Th2 balanc

Relationships between cardiovascular and immunological changes in an experimental stress model

To investigate the relationships between cardiovascular variables (SBP, DBP, and HR) and circulating natural killer (NK) cell numbers, 70 male volunteers were subjected to a rest condition (N = 30) or a stressful laboratory task (N = 40). At baseline, no significant relationships could be demonstrated between the number of NK cells and the cardiovascular variables. Analysis of covariance showed that the stressor induced increases in the number of NK cells, SBP, DBP, and HR. Changes in Nk cell numbers were highly correlated to changes in cardiovascular variables in both the task and the no-task group. These results indicate that there is no relationship between the number of circulating NK cells and cardiovascular levels per se, but that changes in these variables, either stress-induced or under rest conditions, are regulated by a common mechanis